A genetically determined abnormality in the binding of thiamine pyrophosphate to transketolase has been demonstrated in cultured fibroblasts from 4 patients with Wernicke-Korsakoff syndrome, and confirmed in studies of red blood cell transketolase by other groups. Improved techniques for assaying and purifying transketolase from red cells and fibroblasts are being developed. Activity of transketolase, binding of thiamine pyrophosphate, and other properties of this enzymes are being studied in patients with Wernicke-Korsakoff syndrome, neuropathy, alcoholism without frank neurological disease, and controls. These data will indicate the specificity of the anomaly in binding of thiamine-pyrophosphate to transketolase for the Wernicke-Korsakoff syndrome.